Many drugs or drug candidates have been developed for the treatment of various cancers, including some small molecule compounds. However, current treatments for many cancers are not very effective in patients with specific subsets of cancers, or are too toxic in such patients or in general.
Myelodysplastic syndromes (MDS) are a group of diseases that affect the bone marrow and blood. Some types of MDS are mild and easily managed, while other types are severe and life-threatening. Myelodysplastic syndromes (MDS) are rarely cured; most patients never actually complete treatment. The current treatment of MDS is based on the stage and the mechanism of the disease that predominates the particular phase of the disease process. Bone marrow transplantation has been used in patients with poor prognosis or late-stage MDS. Epstein and Slease, 1985, Surg. Ann. 17:125. This type of therapy, however, is both painful for donor and recipient, because of the involvement of invasive procedures and can cause severe and even fatal complications to the recipient, particularly with allogeneic transplant and related Graft Versus Host Disease (GVHD) results. Therefore, the risk of GVHD restricts the use of bone marrow transplantation to patients with otherwise fatal diseases. Further, as most patients are elderly and only a few young MDS patients will have a matched donor, the use of bone marrow transplantation is limited. There remains a need for more effective methods for treating MDS and its related disorders.
Mild MDS can grow more severe over time. It can also develop into a fast-growing, severe leukemia, acute myelogenous leukemia (AML). AML is a subset of leukemia. It is the most common form of adult leukemia (blood cancer) with a <20% survival rate after 5 years and less than 5% if patients are age >65. Current treatments for AML are blunt and harsh chemotherapies (i.e., cytarabine, anthracycliine, etc.) that are not targeted and have limiting off-target toxicities. Thus, there is a severe unmet medical need for distinguishing patients who are potentially sensitive to a certain treatment, and patients who are not.
The present invention meets this need and provides compositions and methods for the effective treatment of cancers.